Physiological function of sigma receptors: Central pharmacological effects of sigma ligands

N-allylnormetazocine (SKF-10047) and related benzomorphans induce psychotomimetic effects in animals and humans, and bind a unique non-opioid receptor, denoted the sigma site. Sigma receptors have been found in the cortical and limbic structures in human postmortem brain: their anatomical distribution is different from phencyclidine (PCP) sites. Sigma receptors regulate not only dopamine, excitatory amino acid and PCP receptors, but also interact neuropeptides. Endogenous sigma ligands are not yet determined. Isolation and cloning of the receptor genes have not yet been successful. Selective loss of cerebral cortical sigma, but not PCP binding sites, has been observed in schizophrenia. A more compelling role for sigma sites in schizophrenia is indicated by the high affinity of some neuroleptic drugs, including haloperidol, for sigma sites. Rimcazole, a weak but selective sigma ligand, has very good clinical efficacy as a neuroleptic agent and has few side effects. Thus, sigma ligands may be useful in the treatment of schizophrenia. The present review describes properties of sigma receptors and its roles in relation to sigma ligands in the regulation of the cental nervous system on the basis of the results of more recent studies.